Project Summary To maintain body core temperature (TCORE) in mammals, the central nervous system thermoregulatory networks respond to skin cooling by increasing brown adipose tissue and shivering thermogenesis, and by reducing heat loss via cutaneous vasoconstriction. However, there are several conditions (e.g., hibernation, torpor, REM sleep) in which these ?standard? thermoregulatory responses to protect TCORE appear to be superseded by a ?thermoregulatory inversion? in which cold exposure causes inhibition of thermogenesis and warm exposure stimulates thermogenesis. We hypothesize that blockade of POA thermoregulatory function is required for the initiation of thermoregulatory inversion and that such paradoxical thermoregulation is governed by a new central thermoregulatory pathway. We will employ in vivo neurophysiological studies in anesthetized rats, a parallel demonstration of thermoregulatory inversion in a free-behaving rat model, and state-of-the-art anatomical studies to understand the relevant neural pathways regulating thermoregulatory inversion. This study will open a new field of research in thermoregulation and will elucidate a new mechanism for a rapid, controllable, stable and reversible induction of hypothermia for the treatment of ischemic stroke, brain trauma and to block persistent, high neurogenic fevers.